Kearney, H.; Rak-Raszewska, A.; Seijas-Gamardo, A.; Escarda-Castro, E.; Wieringa, P.; Moroni, L.; Mota, C.

The field of human induced pluripotent stem cells (hiPSCs) has seen significant progress since the discovery of reprogramming somatic cells using the transcription factors Oct4, Sox2, Klf4, and c-Myc. hiPSCs are similar to embryonic stem cells in a primed state of pluripotency and has the potential to differentiate into any adult human cell type, offering a versatile tool for research and potential therapeutic applications. However, the efficiency of differentiation protocols for generating complex structures with multiple cell types, like kidney organoids, remains a challenge. This study investigates the impact of treating hiPSCs with a low-dose dimethyl sulfoxide to enhance kidney organoid differentiation using a well-established protocol from literature. We found that treating hiPSCs with 1-2% DMSO affects gene expression of pluripotent transcription factors, hiPSC colony morphology, and enhances the expression of key metanephric mesenchyme nephron progenitor marker, SIX2 after 9 days of kidney organoid differentiation. Our findings also suggest that DMSO treatment helps improve hiPSC differentiation protocol efficiency toward the development of tubular kidney organoids. Further research is needed to elucidate the mechanisms underlying these effects and to refine the differentiation process for potential in vitro research applications in biomedical research and drug development.